Etiology and clinical pattern of cervical lymphadenopathy in

SUDANESE JOURNAL OF PAEDIATRICS
2012; Vol 12, Issue No. 1
Original Article from Thesis
Etiology and clinical pattern of cervical
lymphadenopathy in Sudanese children
Jalal Ali Bilal (1, 2), Eltahir M Elshibly (2)
(1) Pediatric department, College of Medicine, Qassim University, Buraidah, Saudi Arabia
(2) Departments of Paediatrics and Child Health. University of Khartoum, Sudan
ABSTRACT
Cervical lymphadenopathy (CLA) is a common
childhood problem in clinical practice which
poses diagnostic difficulties to pediatricians.
The aims of this study were to determine the
causes of CLA in Sudanese children and to
evaluate the value of routine laboratory tests
in determining the etiology. Demographic and
clinical data were prospectively collected from
eighty children with palpable cervical nodes.
Children were then subjected to complete blood
count, ESR, Mantoux test, aspiration cytology
of a lymph node and serological tests for HIV
agglutination test, ELISA for Epstein–Barr
virus and toxoplasma gondii. The age ranged
1-13 years with a mean of 5.8 ±3.1SD years
with no gender difference. Specific etiologies
of CLA were determined in 62.5% of patients.
Ninety five percent of the causes were due to
infectious
mononucleosis
due
Epstein–Barr
virus (13.8%), tuberculous adenitis (10%), acute
adenitis (6.2%), whereas malignancy (Hodgkin’s
lymphoma) constituted 5% of causes of CLA.
The clinical characteristics were insignificantly
associated with the causes of lymphadenopathy
(p>0.05). However, mobile lymph nodes were
significantly
conditions
associated
(P<0.05).
with
inflammatory
Inflammatory
causes
accounted for the majority of the etiologies
whereas Hodgkin’s lymphoma was the only
identified malignancy. Laboratory tests such
as,
ESR, TWBC,
hemoglobin and Mantoux
test should be used in adjunct with cytology and
serology for diagnosis.
Key
words:
Lymphadenopathy,
cervical
lymphadenopathy, etiology, Sudan.
non-specific reactive hyperplasia of lymph
nodes (NSRH) (37.5%), toxoplasmosis (27.5%),
Correspondence to:
Dr Jalal Ali Bilal
Pediatric department, College of Medicine,
Qassim University, PO Box 5566, Postal code 51452,
Buraidah, Saudi Arabia.
Email: [email protected]
How to cite this article:
Bilal JA. Elshibly EM. Etiology and clinical pattern
of cervical lymphadenopathy in Sudanese children.
Sudan J Paediatr 2012;12(1):97-103.
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SUDANESE JOURNAL OF PAEDIATRICS
2012; Vol 12, Issue No. 1
INTRODUCTION
slides stained by H&E and Geimsa stain and
Lymphadenopathy is the disease process of
the lymph nodes that rendering them abnormal
in size and consistency. The etiologies are
multiple; Infection is the most common trigger
for lymph nodes enlargement in children [1].
Cervical lymphadenopathy (CLA) is a common
problem in clinical practice during childhood [2]
and usually poses diagnostic difficulties on the
physicians and looked at with fear by parents.
Approximately 38% to 45% of apparently normal
children have palpable cervical lymph nodes [3].
The aims of this study were to determine the
causes of CLA in Sudanese children and to
evaluate the value of routine laboratory tests in
determining the etiology.
then examined by a cytologist. Five millilitres
of blood were obtained from a peripheral vein
for determination of haemoglobin concentration,
ESR, total and differential white blood cell count
and centrifuged for sera. Sera were used for
analysis for HIV using a particle agglutination
test (Fujirebio inc., Tokyo, Japan), ORTHO
Epstein–Barr virus VCA-IgM antibody ELISA.
Furthermore
gondii
IgM
and IgG antibodies were analysed by ELISA
technology (in vitro test) using special kits by
Alpha Diagnostic International (ADI) - 8491
Abe Lincoln Rd., San Antonio, Texas 78240,
USA. All these serological tests were performed
according to the standards of the manufacturer’s
guidelines.
PATIENTS AND METHODS
Final diagnoses were set on the basis of clinical
This cross-sectional, descriptive study was
conducted in Khartoum Children Emergency
Hospital during the period from January through
December 1998. The population was children
with CLA (lymph node of ≥ 10 millimetres) [1]
aged 1-13 years attending the outpatient clinic.
Patients with cervical abscess or who were
previously investigated for lymphadenopathy
were excluded. Parents of children were briefed
about the study and a written consent was signed
by them. This study was approved by the Research
and Ethics Committee of the Department of
Paediatric, University of Khartoum.
A total of 80 patients with CLA were included in
this study following a pilot study. Demographic
data and the clinical history and examination
details were obtained using a questionnaire. For
every child a thin-needle transcutaneous biopsy
findings, cytology and serology.
Data were entered into SPSS software version
16. Chi square test was used to compare the
difference between categorical data and oneway ANOVA to compare means of laboratory
values in different causes of CLA. The Level of
significance was set at P ≤ 0.05.
RESULTS
We studied 80 children with CLA. The age of
patients ranged 1-13 years with a median of 6
years and a mean of 5.8 ±3.1SD years. Males
were 49 (61.2%) and females were 31(38.2%)
with a ratio of 1.5:1. However, gender difference
was statistically insignificant (P=0.27).
The presentation and the clinical findings
including the affected groups of lymph nodes are
shown in table 1.
of a lymph node was performed by the author
and the aspirate was evenly spread onto 2 glass
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anti-Toxoplasma
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2012; Vol 12, Issue No. 1
Table 1- History and clinical examination findings in children with cervical lymphadenopathy.
Patients (N)
%
History
neck mass
68
85
Fever
57
71.3
Cough
45
57
Loss of weight
44
55
Sore throat
37
46.2
Loss of appetite
33
41.2
Headache
22
27.5
Malaise
15
18.8
Tuberclosis contact
13
16.2
Arthralgia
10
12.5
Earache
10
12.5
Dental caries
8
10
Skin rash
7
8.8
Skin infection
5
6.2
Haemoptysis
2
2.5
Physical examination
Splenomegaly
Hepatomegaly
Mouth ulcers
Impetigo
Otitis media
Affected group of nodes
Anterior cervical triangle
Submandibular
Posterior cervical triangle
Groups other than cervical
Preauricular
The number of palpable cervical lymph nodes in the
patients ranged from 1-10 nodes with a mean number
of 3.5±2 nodes and a mean size of 3.4±1.7 (ranged
1-6) centimeter. The majority of the patients; 96.2%
(n=77) had firm, non-tender (83.8%, n=67) and
mobile nodes (87.5%, n=70).
Specific etiologies of CLA in children in the present study
were determined in 62.5% of patients. Ninety five percent
of these causes were due to inflammatory conditions. These
were, non-specific reactive hyperplasia of lymph nodes
(NSRH) in 37.5% (n=30) patients, toxoplasmosis in 27.5%
15
5
3
3
2
18.8
6.2
3.8
3.8
2.5
69
48
46
21
6
86.2
60
57.5
26.2
7.5
(n=22) patients, infectious mononucleosis due to Epstein–
Barr virus in 13.8% (n=11) patients, tuberculous adenitis in
10% (n=8) patients, acute adenitis in 6.2% (n=5), whereas
malignancy (Hodgkin’s lymphoma) constituted 5% of
causes of CLA.
As shown in table 2, age is not an important
determinant of any of the causes of CLA except for
lymphoma where it was significantly found in the age
group above 10years (p<0.001). However, there was
no significant gender difference within all causes of
CLA (p=0.57).
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SUDANESE JOURNAL OF PAEDIATRICS
2012; Vol 12, Issue No. 1
Table 2- Causes of cervical lymphadenopathy in children according to the age (N=80).
Diagnosis
Age groups
Total
0-5
>5-10
>10-15
Freq
%
Freq
%
Freq
%
NSRH
13
43.3
17
56.7
0
0
30
Toxopalsmosis
10
45.5
10
45.5
2
9
22
Mononucleosis
4
36.4
6
54.5
1
9
11
Tuberculosis
5
62.5
2
25
1
12.5
8
Acute adenitis
4
80
1
20
0
0
5
Lymphoma
1
25
0
0
3
75
4
Total
37
46.25
36
45
7
8.75
80
P
value
0.057
0.995
0.767
0.487
0.284
0.000
0.003
NSRH - nonspecific reactive hyperplasia
The clinical characteristics of lymphadenopathy caused by
the different causes, in this study, with special reference
to the site, number, tenderness and the size of the involved
lymph nodes in the cervical region were insignificantly
associated with the causes of lymphadenopathy (p>0.05).
However, mobile lymph nodes were significantly associated
with acute adenitis (p=0.002) and toxoplasmosis (p=0.031).
A one-way ANOVA between subjects was conducted to
compare the values of erythrocyte sedimentation rate,
hemoglobin concentration, total and differential white cell
count and mantoux test in causes of CLA in this study.
Taken together, these laboratory values, as diagnostic tools,
have no significant association with the causes of CLA
(p>0.05) (Table 3).
Table 3- One way ANOVA comparing means of laboratory values in etiologies of cervical
lymphadenopathy in children (N=80).
Differential WCC
(% of total WCC)
Causes of LA
NSRH
Tuberculosis
Acute adenitis
Toxoplasmosis
Mononucleosis
Lymphoma
F
P
Mantoux test
ESR (mean±SD) Hb
WCC**
(mean±SD) mm
mm/hour
(mean±SD) (mean±SD)
Mg/dl
Cells/mm³
7.96±2.4
10.12±9.1
3.4±4.6
7.5±1.5
8.6±1.4
5.5±1.0
1.987
0.09
62.6±3.5
87±2.8
61.4±3.2
60.6±3.0
60.3±2.5
50.7±8.3
1.140
0.34
10.06±1.87
8.9±1.7
9.9±2.0
9.7±2.4
9.9±2.1
9.8±0.6
0.449
0.81
7790±4591
7275±2686
12200±1047
7141±3247
7672±3753
5775±1629
1.253
0.29
Neutrophls
46
52
50
43
44
64
1.639
0.16
Lymphocytes
52
47
48
55
53
36
1.599
0.17
Eosinophils
2
1
2
2
3
0
0.865
0.87
ESR - erythrocyte sedmentation rate, F - F test value, Hb - hemoglobin, LA - lymphadenopathy, NSRH Nonspecific reactive hyperplasia, P - P test value, WCC - white cell count
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SUDANESE JOURNAL OF PAEDIATRICS
DISCUSSION
2012; Vol 12, Issue No. 1
The workup of palpable lymph nodes is a common
clinical task for the general practitioners and the
pediatricians. Most of the causes of CLA are benign
and may resolve spontaneously [4]. It can be, on
the other hand, a sign of malignancy or systemic
disease, thus understanding the differential causes is
of paramount importance for evaluation and precise
timely diagnosis for the possibility of a yield of
around 15.8% for serious conditions in one series [5].
Specific causes of lymphadenopathy, in this study,
could be determined in 62.5% of patients. Nonspecific reactive hyperplasia of lymph nodes (NSRH)
is defined as a benign reversible enlargement of the
lymph node resulting from the proliferation of part or
all of its cellular components [6]. NSRH was found
in 37.5% of patients with CLA in this study, much less
than the 60% reported by Citak et al. [7], and more
than Ayugi et al. who reported 29 %. Ranking as first
as of the benign causes in this study, NSRH is known
to be of unknown cause and the most common in
literature [8]. The difference in occurrence is possibly
attributed to different methods of identification and
definition of NSRH.
Enlarged lymph nodes are the most frequently
observed clinical form of toxoplasmosis in humans
[9]. Almost 28 % of patients with enlarged cervical
lymph nodes had acquired toxoplasmosis in the
present study, a much higher rate than the 10% rate
reported in literature [1]. The seropositive prevalence
of toxoplasma antibodies was historically high (61%)
among Sudanese population [10]. In another African
country it was found to be 46% [11]. This may be
attributed to consumption of raw animal products
and it is known that infection associated with cervical
adenopathy is usually acquired via the oral route by
consumption of meat- or milk-containing cysts or
oocytes [1].
Infectious mononucleosis caused by Epstein–Barr
virus was found in 13.8% of patients with CLA in
this series. This was similar to literature as Citak
et al reported 13.4% among children with benign
lymphadenopathy [7], whereas Abdel-Aziz et al
reported a figure of 15% [12].
Lymphadenopathy due to tuberculosis was found
in 10% of patients in this study which is lower than
the report from Greece by Papadopouli et al who
reported a rate of 12 % and even much lower than
the 21.4% rate of a similar study from Kenya [13].
This may be attributed to the low specificity of fine
needle aspiration cytology for the diagnosis of the
granulomatous lesion of tuberculosis that may have
a false negative rate of 38%. FNAC would have been
more yielding if combined with PCR, a costly tool of
diagnosis in a developing country [14].
Cervical lymph node infection, acute or sub-acute is
frequent and is usually due to viral causes and many
bacteria. This study reported 6.2% acute adenitis as a
cause of CLA. We did not include complications of
acute adenitis, such as abscess in the sample nor did
we ascertain bacteremia, viremia or aspirate culture.
This may underestimate the prevalence of acute
adenitis in pediatric population as Ayugi et al reported
abscess as the commonest cause representing 33%
of the inflammatory causes of lymphadenopathy [8].
However when cases of NSRH, as inflammatory
causes, are added to the 6.2% of acute adenitis the
figure will be 43.7% which is more or less comparable
to literature reports [8].
Lymphoma cases in this study, all Hodgkin’s, were
found in 5% of patients with CLA. These cases were
confirmed later by excisional biopsy and referred to
the oncologist. Our figure is comparable to the report
of Citak et al [7] but higher than the 2% reported by
Papadopouli et al. [13], their low prevalence might
be attributed to their method of diagnosis and not all
patients underwent biopsy of any type.
Only lymphoma was associated with lymphadenopathy
in children 10 years and older. Age and gender was
not a determinant in any the other causes of CLA in
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this study.
This study did not find any relationship between lymph
nodes size, site, number, tenderness and etiology.
However, mobile lymph nodes were associated
with acute adenitis and toxoplasmosis. Srouji et al.,
reported an association of tenderness, mobility and
fluctuating size of the nodes with NSRH but their
sample was too small to draw conclusive guidelines
[5].
The series of investigations done in this study i.e.
ESR, hemoglobin concentration, total and differential
white cell count showed great inconsistency with
different means and ranges for each patient in the
study. This observation is similar to Srouji et al results
[5] but reported by Niedzielska et al [4] as helpful in
the differential diagnosis.
CONCLUSION
Specific etiologies of CLA in children can be
determined in 62.5% of patients using FNSC and
serological tests, indicating the usefulness of FNAC
and serology, especially in limited-resource countries.
Inflammatory causes accounted for the majority of the
etiologies. These are NSRH, acquired toxoplasmosis,
Epstein–Barr virus-infectious mononucleosis and
tuberculosis. Hodgkin’s lymphoma was the only
identified malignancy among the studied cases.
Lymph node site and size are not helpful in diagnosis
whereas mobility is associated with inflammatory
causes.
Laboratory tests such as, ESR, TWBC, hemoglobin
and mantoux Test should be used in adjunct with
cytology and serology for diagnosis.
ACKNOWELDEGEMENT
The authors would like to thank Dr. Adel M. Hussein
for examining the cytology, Dr Isam M Elkhidir and
Dr Maowia Mukhtar for their valuable contribution.
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‫*٭‬Original article from Clinical MD in Paediatrics and Child Health thesis, The University of
Khartoum (U of K), 1998 by Jalal Ali Bilal , MB BS (U of Juba). Supervisor: Dr Eltahir M Elshibly,
MB BS, MPCH, (U of K), FRCPCH .
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